Significance Attenuated measles vaccine is one of the most safe and effective vaccines available. However, because maternal antibody can neutralize the vaccine virus in the infant, it cannot be administered before 6 to 9 months of age. Objectives To develop a safe and effective vaccine for measles that can be given at birth. Last year, recombinant BCG expressing measles nucleoprotein did not prevent infection but did protect infant monkeys from measles pneumonia. Results Newborn rhesus macaques were immunized with vaccinia viruses expressing measles hemagglutinin and fusion proteins, using the WR strain of vaccinia (wrH&F) or modified vaccinia virus Ankara (mvaH&F). The infants were boosted at 3 months and challenged intranasally with measles virus at 6 months. Half of the newborn monkeys received measles immune globulin (MIG) prior to the first immunization. Vaccination induced high-titer neutralizing antibody in infants that did not receive MIG, and low-titer antibody in the monkeys with MIG. Three levels of protection were observed after measles virus challenge. 1) No clinical signs of measles and no virus recovery. This response was observed in infants vaccinated with wrH+F without MIG (3 of 3 infants), mvaH+F without MIG (1/4) or wrH+F with MIG (1/4). 2) No signs of measles but low-level viremia. This response occurred in infants vaccinated with mvaH+F without MIG (3/4) and mvaH+F with MIG (1/4). 3) Skin rash and viremia similar to control monkeys. This response occurred with wrH+F with MIG (3/4) and mvaH+F with MIG (3/4). Thus vaccinia virus expressing measles H and F genes were effective in preventing measles in infant monkeys, but these vectors would not be effective in the presence of maternal antibody at birth. Future Directions Other vectors that can prime strong T cell responses to measles antigens in infant monkeys will be compared with the BCG vaccine vector. KEYWORDS measles, vaccine, infant health